scholarly journals Organocatalytic atroposelective heterocycloaddition to access axially chiral 2-arylquinolines

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Gongming Yang ◽  
Shaofa Sun ◽  
Zhipeng Li ◽  
Yuhan Liu ◽  
Jian Wang
Keyword(s):  
Drug Discovery ◽  
Asymmetric Synthesis ◽  
Vital Role ◽  
Optically Active ◽  
Enantioselective Synthesis ◽  
Chiral Amine ◽  
New Class ◽  
Axially Chiral ◽  
High Yields

AbstractAxially chiral heterobiaryls play a vital role in asymmetric synthesis and drug discovery. However, there are few reports on the synthesis of atropisomeric heterobiaryls compared with axially chiral biaryls. Thus, the rapid enantioselective construction of optically active heterobiaryls and their analogues remains an attractive challenge. Here, we report a concise chiral amine-catalyzed atroposelective heterocycloaddition reaction of alkynes with ortho-aminoarylaldehydes, and obtain a new class of axially chiral 2-arylquinoline skeletons with high yields and excellent enantioselectivities. In addition, the axially chiral 2-arylquinoline framework with different substituents is expected to be widely used in enantioselective synthesis.

scholarly journals Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

2017 ◽  
Vol 13 ◽  
pp. 1518-1523 ◽  
Author(s):  
Ryota Miyaji ◽  
Yuuki Wada ◽  
Akira Matsumoto ◽  
Keisuke Asano ◽  
Seijiro Matsubara
Keyword(s):  
Asymmetric Synthesis ◽  
Functional Groups ◽  
Enantioselective Synthesis ◽  
Chiral Compounds ◽  
Axially Chiral ◽  
Electrophilic Bromination ◽  
Mechanistic Investigations ◽  
Molecular Skeleton

Bifunctional organocatalysts bearing amino and urea functional groups in a chiral molecular skeleton were applied to the enantioselective synthesis of axially chiral benzamides via aromatic electrophilic bromination. The results demonstrate the versatility of bifunctional organocatalysts for the enantioselective construction of axially chiral compounds. Moderate to good enantioselectivities were afforded with a range of benzamide substrates. Mechanistic investigations were also carried out.

Enantioselective synthesis of chiral α,β-unsaturated γ-substituted butyrolactams by organocatalyzed direct asymmetric vinylogous Michael addition of α,β-unsaturated γ-butyrolactam to 2-enoylpyridines

2016 ◽  
Vol 14 (27) ◽  
pp. 6568-6576 ◽  
Author(s):  
Zhen-Hua Wang ◽  
Zhi-Jun Wu ◽  
Deng-Feng Yue ◽  
Yong You ◽  
Xiao-Ying Xu ◽  
...  
Keyword(s):  
Michael Addition ◽  
Optically Active ◽  
Enantioselective Synthesis ◽  
High Yields

Approach providing a series of optically active α,β-unsaturated γ-substituted butyrolactams in high yields with excellent diastereo- and enantioselectivities.

Enantioselective Synthesis of 1-Substituted 1,2,3,4-Tetrahydroisoquinolines through 1,3-Dipolar Cycloaddition by a Chiral Phosphoric Acid

Synlett ◽  
2019 ◽  
Vol 30 (13) ◽  
pp. 1541-1545 ◽  
Author(s):  
Yuan Jin ◽  
Yasuhiro Honma ◽  
Hisashi Morita ◽  
Masamichi Miyagawa ◽  
Takahiko Akiyama
Keyword(s):  
Phosphoric Acid ◽  
Asymmetric Synthesis ◽  
Vinyl Ether ◽  
31P Nmr ◽  
Cycloaddition Reaction ◽  
Enantioselective Synthesis ◽  
Dipolar Cycloaddition ◽  
New Approach ◽  
Chiral Phosphoric Acid ◽  
High Yields

A new approach is described for the asymmetric synthesis of 1-substituted 1,2,3,4-tetrahydroisoquinolines that is based on the enantioselective 1,3-dipolar cycloaddition reaction of a nitrone and a vinyl ether in the presence of a chiral phosphoric acid that gives the chiral tetrahydroisoquinolines in high yields and with high enantioselectivities. 1H and 31P NMR analyses of the mixture of nitrone and chiral phosphoric acid suggest the formation of a 1:1 complex.

The synthesis of optically active N–C axially chiral tetrahydroquinoline and its response to an acid-accelerated molecular rotor

2015 ◽  
Vol 51 (56) ◽  
pp. 11229-11232 ◽  
Author(s):  
Yuya Suzuki ◽  
Masato Kageyama ◽  
Ryuichi Morisawa ◽  
Yasuo Dobashi ◽  
Hiroshi Hasegawa ◽  
...  
Keyword(s):  
Optically Active ◽  
Molecular Rotor ◽  
Chiral Amine ◽  
Axially Chiral ◽  
New Type

The synthesis of an optically active N–C axially chiral amine and its response to a new type of acid-accelerated molecular rotor were achieved.

scholarly journals Organocatalysts for enantioselective synthesis of fine chemicals: definitions, trends and developments

2015 ◽  
Author(s):  
Chiara Palumbo
Keyword(s):  
Asymmetric Catalysis ◽  
Scientific Community ◽  
Organic Molecules ◽  
Optically Active ◽  
Enantioselective Synthesis ◽  
Fine Chemicals ◽  
Organic Transformations ◽  
Small Organic Molecules ◽  
Substrate Activation ◽  
High Yields

Organocatalysis, that is the use of small organic molecules to catalyse organic transformations, has been included among the most successful concepts in asymmetric catalysis and it has been used for the enantioselective construction of C-C, C-N, C-O, C-S, C-P, and C-halide bonds. Since the seminal works in early 2000, the scientific community has been paying an ever-growing attention to the use of organocatalysts for the synthesis, with high yields and remarkable stereoselectivities, of optically active fine chemicals of interest for the pharmaceutical industry. A brief overview is here presented about the two main classes of substrate activation by the catalyst: covalent organocatalysis and non-covalent organocatalysis, with a more stringent focus on some recent outcomes in the field of the latter and of hydrogen-bond-based catalysis. Finally, some successful examples of heterogenisation of organocatalysts are also discussed, in the view of a potential industrial exploitation.

scholarly journals Organocatalysts for enantioselective synthesis of fine chemicals: definitions, trends and developments

2015 ◽  
Keyword(s):  
Asymmetric Catalysis ◽  
Scientific Community ◽  
Organic Molecules ◽  
Optically Active ◽  
Enantioselective Synthesis ◽  
Fine Chemicals ◽  
Organic Transformations ◽  
Small Organic Molecules ◽  
Substrate Activation ◽  
High Yields

<p>Organocatalysis, that is the use of small organic molecules to catalyse organic transformations, has been included among the most successful concepts in asymmetric catalysis and it has been used for the enantioselective construction of C-C, C-N, C-O, C-S, C-P, and C-halide bonds. Since the seminal works in early 2000, the scientific community has been paying an ever-growing attention to the use of organocatalysts for the synthesis, with high yields and remarkable stereoselectivities, of optically active fine chemicals of interest for the pharmaceutical industry. A brief overview is here presented about the two main classes of substrate activation by the catalyst: covalent organocatalysis and non-covalent organocatalysis, with a more stringent focus on some recent outcomes in the field of the latter and of hydrogen-bond-based catalysis. Finally, some successful examples of heterogenisation of organocatalysts are also discussed, in the view of a potential industrial exploitation.</p>

Total Synthesis of Axially-Chiral Cannabinols: A New Platform for Cannabinoid-Based Drug Discovery

2019 ◽  
Author(s):  
Primali Navaratne ◽  
Jenny Wilkerson ◽  
Kavindri Ranasinghe ◽  
Evgeniya Semenova ◽  
Lance McMahon ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Total Synthesis ◽  
Ground State ◽  
Chemical Space ◽  
Modern Medicine ◽  
The Novel ◽  
Pharmaceutical Development ◽  
Bioactive Component ◽  
Axially Chiral ◽  
New Directions

<div> <div> <div> <p>Phytocannabinoids, molecules isolated from cannabis, are gaining attention as promising leads in modern medicine, including pain management. Considering the urgent need for combating the opioid crisis, new directions for the design of cannabinoid-inspired analgesics are of immediate interest. In this regard, we have hypothesized that axially-chiral-cannabinols (ax-CBNs), unnatural (and unknown) isomers of cannabinol (CBN) may be valuable scaffolds for cannabinoid-inspired drug discovery. There are multiple reasons for thinking this: (a) ax-CBNs would have ground-state three-dimensionality akin to THC, a key bioactive component of cannabis, (b) ax-CBNs at their core structure are biaryl molecules, generally attractive platforms for pharmaceutical development due to their ease of functionalization and stability, and (c) atropisomerism with respect to phytocannabinoids is unexplored “chemical space.” Herein we report a scalable total synthesis of ax-CBNs, examine physical properties experimentally and computationally, and provide preliminary behavioral and analgesic analysis of the novel scaffolds. </p> </div> </div> </div>

Recent Development of Small Molecule Glutaminase Inhibitors

2018 ◽  
Vol 18 (6) ◽  
pp. 432-443 ◽  
Author(s):  
Minsoo Song ◽  
Soong-Hyun Kim ◽  
Chun Young Im ◽  
Hee-Jong Hwang
Keyword(s):  
Small Molecule ◽  
Cell Metabolism ◽  
Phase 1 ◽  
Vital Role ◽  
Glutamine Metabolism ◽  
Inhibition Mechanism ◽  
Tumor Cell Growth ◽  
X Ray ◽  
New Class ◽  
Preclinical And Clinical Studies

Glutaminase (GLS), which is responsible for the conversion of glutamine to glutamate, plays a vital role in up-regulating cell metabolism for tumor cell growth and is considered to be a valuable therapeutic target for cancer treatment. Based on this important function of glutaminase in cancer, several GLS inhibitors have been developed in both academia and industry. Most importantly, Calithera Biosciences Inc. is actively developing the glutaminase inhibitor CB-839 for the treatment of various cancers, and it is currently being evaluated in phase 1 and 2 clinical trials. In this review, recent efforts to develop small molecule glutaminase inhibitors that target glutamine metabolism in both preclinical and clinical studies are discussed. In particular, more emphasis is placed on CB-839 because it is the only small molecule GLS inhibitor being studied in a clinical setting. The inhibition mechanism is also discussed based on X-ray structure studies of thiadiazole derivatives present in glutaminase inhibitor BPTES. Finally, recent medicinal chemistry efforts to develop a new class of GLS inhibitors are described in the hopes of providing useful information for the next generation of GLS inhibitors.

Engineering the large pocket of an (S)-selective transaminase for asymmetric synthesis of (S)-1-amino-1-phenylpropane

2021 ◽  
Author(s):  
Youyu Xie ◽  
Feng Xu ◽  
Lin Yang ◽  
He Liu ◽  
Xiangyang Xu ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
Environmentally Benign ◽  
Chiral Amine ◽  
Synthesis Route

Amine transaminases offer an environmentally benign chiral amine asymmetric synthesis route.

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